Dataset Information

Peritoneal Cell-Derived Exosomes: Novel Mediators of T Cell Activation and Vaccine Potency in Fish

ABSTRACT: Exosomes are small extracellular vesicles that play significant roles in cell communication and immune modulation. When considering adaptive immunity, exosomes have been proposed to be involved in T and B cell development, antigen presentation, as well as the cross-presentation of antigens. While the potential of exosomes to carry vaccine-relevant antigens has been discussed, their intrinsic properties in activating adaptive immune responses have not yet been fully addressed. To explore these roles further, this study utilizes a fish model to examine the detailed effects of exosomes. We demonstrate that the peritoneal cells derived exosomes (PDEs), which fuse with cells in the peritoneum, carry and transport antigen presentation molecules locally. Additionally, PDEs are transferred from the peritoneum and accumulate in critical lymphoid organs, including the head kidney and spleen. Notably, PDEs effectively promoted Cd4-1+ and Cd4-2+ T cells activation in both in vivo and in vitro settings following exposure of cells to the PDEs. The experimental outcomes have indicated an increased level of Mhcii+ and Cd80/86+ exosomes secreted from peritoneal cells of fish vaccinated with Vibrio anguillarum via intraperitoneal injection, accompanied by the carriage of T cell-associated RNA and miRNA cargos. Moreover, the intraperitoneal injection of endogenous exosomes derived from Vibrio anguillarum-elicited cells enhanced vaccine potency by promoting antibody production. This study provides a novel avenue wherein exosomes are directly involved in vaccine-induced immunity, as evidenced in a lower vertebrate. It is plausible that such events and processes may also prevail in higher vertebrates, such as in humans.

INSTRUMENT(S):

ORGANISM(S): Paralichthys Olivaceus

TISSUE(S): Peritoneal Fluid

SUBMITTER: xueyan shi

LAB HEAD: Xueyan Shi

PROVIDER: PXD059066 | Pride | 2026-04-06

REPOSITORIES: pride

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Peritoneal exosomes mediate activation of CD4<sup>+</sup> T cells and enhancement of vaccine efficacy in teleost.

Shi Xueyan X Jiang Lixia L Ye Miao M Yanglang Arat A Mikkelborg Marie Kristin MK Tang Xiaoqian X Xing Jing J Sheng Xiuzhen X Zhan Wenbin W Dalmo Roy Ambli RA Chi Heng H

Cell communication and signaling : CCS 20260221 1

PMID: 41721417

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Project description:The liver fluke Fasciola hepatica is an economically important pathogen of livestock. Fasciolosis in humans is an important re-emerging zoonosis, with 180 million people at risk. Development of novel control strategies requires an understanding of parasite virulence and tissue invasion, and of how the parasite evades and modulates the immune response during early infection. A combination of immunological and proteomic analyses was employed to investigate the peritoneal fluid of sheep infected with F. hepatica to characterise early tissue invasion and liver pathogenesis. At 18 days post-infection (dpi), histopathology of sheep liver showed white necrotic foci/tracts indicative of F. hepatica migration. Within the peritoneal fluid of infected animals, specific F. hepatica antigen FhCL1 antibodies coincided with an intense innate and adaptive cellular immune response, with increasing numbers of total leukocytes and a marked eosinophilia (49%). Cytokine qPCR analysis revealed IL-10, IL-12, IL-13, IL-23 and TGFβ were elevated but not statistically significant at 18 dpi compared to uninfected sheep indicating that whilst the immune response is developing it has not polarised to the Th2 type associated with chronic fasciolosis. Proteomic analysis of the peritoneal fluid identified 178 proteins, with 25 proteins more highly expressed in the infected animals, based on fold changes in protein concentration compared to the uninfected animals. Components of the liver extracellular matrix, including collagen, periostin and the adhesion protein, VCAM-1, exhibited increased expression associated with early fasciolosis, which may be important in signalling host immune responses to tissue damage. In early F. hepatica infection cellular infiltration with marked eosinophilia, adaptive immune responses and products of liver pathology are evident in the peritoneum. Although cytokine responses are developing they are mixed and not yet polarised to a Th2-type. We have characterised biomarkers of parasite-induced liver damage which could be exploited for diagnosis, and vaccine development aimed at reducing/preventing liver pathology.

Project description:Peritoneal dialysis (PD) is the worldwide recognized preferred dialysis treatment for children affected by end-stage kidney disease (ESKD). However, due to the unphysiological composition of PD fluids, the peritoneal membrane (PM) of these patients may undergo structural and functional alterations, which may cause fibrosis. Several factors may accelerate this process and primary kidney disease may have a causative role. In particular, patients affected by corticoresistant primary focal segmental glomerulosclerosis), a rare glomerular disease leading to nephrotic syndrome and ESKD, seem more prone to develop peritoneal fibrosis. The mechanism causing this predisposition is still unrecognized. To better define this condition, we carried out, for the first time, a new comprehensive comparative proteomic mass spectrometry analysis of mesothelial exosomes from peritoneal dialysis effluent (PDE) of 6 pediatric patients with focal segmental glomerular sclerosis (FSGS) versus 6 patients affected by other primary renal diseases (No FSGS). Our omic study demonstrated that, despite the high overlap in the protein milieu between the two study groups, machine learning allowed a complete distinction of the whole proteomic exosome mesothelial content of FSGS versus No FSGS (with 100% accuracy). Out of the 2490 identified proteins, 40% (995) were involved in epithelial-mesenchymal transition (EMT)/fibrosis and in the transforming growth factor-β pathway. Additionally, the Weight Gene Co-expression Network Analysis algorithm identified that some of the discriminative proteins (TIMP1, CTHRC1, SPARC, CHMP4B, COL5A2, ANXA13, FNC2 and CENP-E) were also highly correlated to PD vintage, fibrosis, EMT and non-neoplastic PM disease. All together our data demonstrated that mesothelial cells of FSGS patients are more prone to activate a pro-fibrotic machinery with exosomes having a primary role in this process. Moreover, they indicated that identified FSGS-associated elements in mesothelial exosome protein could be employed as potential new biomarkers of mesothelial integrity. Finally, our results highlighted that in FSGS patients particular attention should be paid to use more biocompatible dialysis solution, reduce the length of time on PD and personalize PD regimens to minimize the risk of rapid loss of PM function or development of encapsulating peritoneal sclerosis.

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Dataset Information

Peritoneal Cell-Derived Exosomes: Novel Mediators of T Cell Activation and Vaccine Potency in Fish

Dataset's files

Publications

Peritoneal exosomes mediate activation of CD4<sup>+</sup> T cells and enhancement of vaccine efficacy in teleost.

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Dataset Information

Peritoneal Cell-Derived Exosomes: Novel Mediators of T Cell Activation and Vaccine Potency in Fish

Dataset's files

Publications

Peritoneal exosomes mediate activation of CD4&lt;sup&gt;+&lt;/sup&gt; T cells and enhancement of vaccine efficacy in teleost.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Peritoneal exosomes mediate activation of CD4<sup>+</sup> T cells and enhancement of vaccine efficacy in teleost.